Mapping The Structural Connectome in Autism

Autism and agenesis of the corpus callosum (AgCC) are distinct conditions – the first is behavioral while the second anatomical. Yet about 40% of people born with AgCC show clear indications of autism. Diffusion tractography is a 3D rendering technique that uses data from diffusion tensor imaging (DTI), to map out cortical connections. DTI is basically a refinement of standard MRI which can additionally measure the diffusion of water within tracts of axons. A collaborative effort at UCSF and Berkeley has now analyzed the tractography data for an AgCC study group using network mapping techniques borrowed from mathmatics. Their results now add much needed rigor to previous efforts to structurally define behavior.

Prior imaging studies of Kim Peek (1951-2009), a.k.a. the Rain Main, firmly established the casual association of AgCC to autism. When the midline parts of the brain fail to develop, as happens in AgCC, the axons which normally would travel to the opposite hemisphere will seek out new targets closer to home. The California researchers asked the following simple question: is the lack of inter-hemispheric connectivity consistently associated with unique intra-hemispheric connections? Indeed they found that it is.

To generate a control data, the researchers simulated a “virtual callostomy” sample set in which the callosal connections were removed. When they compared the control group with the natural-born AgCCs, they found that there was significantly greater variability according to their network measure in the AgCC group. They also found that several of the major axon tracts, in particular one known as the cingulum bundle, had significantly reduced connectivity. The cingulum bundle is closely associated with the limbic system of the brain, and as it generally runs along the midline, it might be expected to be part of the larger AgCC anatomical variation.

Both autism and AgCC are now increasingly associated to particular genetic predispositions. In animal studies, genetic manipulations are revealing specific determinants of cortical connectivity. For example, it was just demonstrated that neurons which normally project across the callosum can be given new instructions to instead grow downward to areas deeper in the brain. The potential to observe this kind of genetic variance firsthand now presents itself, at least in theory.

We obviously have not yet seen the full predictive power of network analysis brought to bear. It would be worthwhile if future studies could specifically associate regions of high local connectivity, lets say, with cortical gyri (the convex parts of the brain surface), and associate more divergent, longer range connectivity with the sulci (the concave parts). This would just be an example of a common sense hypothesis based on trying to fit axons into the observed geometry,

For the moment it may be wise that the researchers presented concepts that also can be collaborated by other kinds of studies, as it gives their technique more credibility. Cautionary tales to the interpretation of this kind of diffusion-based data have been raised previously — 25 of them to be exact – but as they become more commonplace, the emerging field of connectomics, and its behavioral associations, will be the direct benefactors.